Organic Chemistry II

The course aims to provide a critical and scientific mentality and rational use of mnemonic abilities, favoring the ability to apply theoretical knowledge to problem-solving.

This means overcoming the limit of mere "mnemonic repetition" of concepts that, in doing so, would be aimed at simple learning. Critical and scientific mentality at the same time constitute a high-level objective; it requires a synthesis between mental operation and actual realization: the first is expressed in the design of an experiment, in the rational-intuitive control of the execution and calculation phases and the evaluation phase of the results; the second is expressed in the actual execution of the experiment, even at the virtual level.

Therefore, at the end of the course, the student must be able to:

D1 KNOWLEDGE AND UNDERSTANDING ABILITY

• Know in-depth the reactivity of new classes of organic compounds and the reaction mechanisms through which they react.

• Illustrate the criteria that allow to carry out processes with a pronounced chemical, position, and stereochemical selectivity.

D2 ABILITY TO APPLY KNOWLEDGE AND UNDERSTANDING

• Identify the nature of the synthetic process to which the organic molecules are subjected based on the described reaction conditions.

• Correctly describe the reaction mechanism for the related processes.

• Discuss the nature of the selective processes that these mechanisms involve.

D3 AUTONOMY OF JUDGMENT

• Choose the most suitable reagents to carry out the required synthetic process with the desired selectivity degree.

• Use the most efficient method available to perform the synthesis of even multi-functionalized structures.

D4 COMMUNICATION SKILLS

• Communicate, using appropriate technical-scientific terminology, with the teacher and experts in the subject of study.

• Competently discuss, even in the context of an oral examination, the synthetic techniques learned.

D5 LEARNING SKILLS

• Find and learn the information, new compared to those provided during the training activity, necessary to broaden the knowledge on topics more or less correlated with those covered by the course.

• Understand and process the contents of scientific publications containing the results of new research.

• Use the knowledge acquired to make it easier to understand topics related to organic chemistry delivered in other educational activities.

The course activities consist of lectures and classroom exercises. To these will be added some "case studies" concerning molecules of chemical-pharmaceutical interest. The student must actively participate in discussing the topics presented and, in particular, in the case studies.

Should teaching be carried out in mixed mode or remotely, it may be necessary to introduce changes to previous statements in line with the program planned and outlined in the syllabus.

Prerequisites: Organic Chemistry 1.

Acid-base properties of organic compounds, basic stereochemistry, properties and reactivity of organic chemistry functional groups.

Knowledge of an adequate study method; the following sites and readings are recommended:

• http://studenti.unimi.it/studentestrategico/metodo/index.htm
• http://helpmetodo.altervista.org/
• http://host.uniroma3.it/docenti/boylan/misc/studi_6r.pdf

Compulsory attendance according to the rules of the teaching regulations of the CdS in CTF is reported in the following link.

The course consists of 3 modules, corresponding to 9 credits, of which 7 lectures and 2 classroom exercises; these last will be carried out at the end of the third module.

To allow the student to follow the topics covered without difficulty and to find them quickly and effectively, a program has been drawn up that strictly follows the general index of the Bruice “Organic Chemistry” and the Clayden “Organic Chemistry”; the chapters and teaching units related to the latter are highlighted in red.

 MODULE 1. Bioorganic compounds

20. The organic chemistry of carbohydrates

Classification of carbohydrates - The d and l notation - Configuration of aldoses - Configuration of ketoses - Reactions of monosaccharides in basic solution - Reduction reactions of monosaccharides - Chain elongation: the modified Kiliani-Fischer synthesis (Serianni-Barker) - Shortening of the chain: the degradation of Wohl - Monosaccharides form cyclic hemiacetals - Glucose is the most stable of the aldohexoses - Formation of glycosides - The anomeric effect - Reducing and non-reducing sugars - Formation of Cyclic Ethers, Esters and Acetals - Aglycones - Disaccharides - Polysaccharides.

Paragraphs: 20.1-20.8 and 20.10-20.16; lecture notes

21. Amino acids, peptides, and proteins

Nomenclature of amino acids - Configuration of amino acids - Acid-base properties of amino acids - The isoelectric point - Separation of amino acids - Methods of synthesis of amino acids - Resolution of a racemic mixture of amino acids - Peptide bonds and disulfide bonds - Some interesting peptides - Synthesis strategies peptide - Automated peptide synthesis - Introduction to the structure of proteins - How to determine the primary structure of a polypeptide or protein.

Paragraphs: 21.1–21.13

 

MODULE 2. Special topics

27. Synthesis polymers

There are two main classes of synthetic polymers - Introduction to chain growth polymers - Free radical polymerization - Teflon: an accidental discovery - Recycling codes - Cationic polymerization - Anionic polymerization - Ring-opening polymerization – Stereochemistry of polymerization • Ziegler-Natta – Polymerization of dienes – Copolymers – Introduction to polymers for staged growth – Classes of polymers for staged growth – Designing a polymer – Physical properties of polymers – Recycling of polymers – Biodegradable polymers.

Paragraphs: 27.1–27.14

8/28/34/35. Periciclyc reactions

The three types of pericyclic reactions: Electrocyclic reactions, cycloaddition and sigmatropic transpositions – Molecular orbitals and symmetry of the orbitals – Electrocyclic reactions – Cycloaddition reactions – Sigmatropic transpositions – A new sort of reaction – General description of the Diels-Alder reaction – Diels-Alder: a 1,4 addition reaction – Retrosynthetic analysis of the Diels-Alder reaction – The frontier orbital description of cycloadditions – Regioselectivity in Diels-Alder reactions – The Woodward-Hoffmann description of the Diels-Alder reaction – Trapping reactive intermediates by cycloadditions – Other thermal cycloadditions – Photochemical [2 + 2] cycloadditions – Thermal [2 + 2] cycloadditions – Making five-membered rings: 1,3-dipolar cycloadditions – Sigmatropic rearrangements – Orbital descriptions of [3,3]-sigmatropic rearrangements – The direction of [3,3]-sigmatropic rearrangements – [2,3]-Sigmatropic rearrangements – Sigmatropic hydrogen and carbon shifts – Electrocyclic reactions.

Paragraphs: 8.14, 8.15 and 28.1–28.5; Chapters 34 and 35; lecture notes

36. Participation, rearrangement, and fragmentation

Neighbouring groups can accelerate substitution reactions – Rearrangements occur when a participating group ends up bonded to a different atom – Carbocations readily rearrange – The pinacol rearrangement – The dienone-phenol rearrangement – The benzylic acid rearrangement – The Favorskii rearrangement – Migration to oxygen: the Baeyer–Villiger reaction – The Beckmann rearrangement – Polarization of C–C bonds helps fragmentation – Fragmentations are controlled by stereochemistry – Ring expansion by fragmentation – Controlling double bonds using fragmentation – The synthesis of nootkatone: fragmentation showcase.

11/38. Synthesis and reactions of carbenes

Diazomethane makes methyl esters from carboxylic acids – Photolysis of diazomethane produces a carbene – How do we know that carbenes exist? – Ways to make carbenes – Carbenes can be divided into two types – How do carbenes react? – Carbenes react with alkenes to give cyclopropanes – Insertion into C–H bonds – Rearrangement reactions – Nitrenes are the nitrogen analogues of carbenes – Alkene and alkyne metathesis.

Paragraph: 11.5; Chapter 38

11/40. Organometallic chemistry of palladium, boron, tin, rhodium, and ruthenium

Palladium Catalyzed Coupling Reactions – Grubbs, Schrock, Suzuki, and Heck Receive Nobel Prize – Transition metals extend the range of organic reactions – The 18 electron rule – Bonding and reactions in transition metal complexes – Palladium is the most widely used metal in homogeneous catalysis – The Heck reaction couples together an organic halide or triflate and an alkene – Cross-coupling of organometallics and halides – Allylic electrophiles are activated by palladium(0) – Palladium-catalysed amination of aromatic rings – Alkenes coordinated to palladium(II) are attacked by nucleophiles – Palladium catalysis in the total synthesis of a natural alkaloid – An overview of some other transition metals.

Paragraph: 11.4; Chapter 40

 

39. Determining reaction mechanisms

There are mechanisms and there are mechanisms – Determining reaction mechanisms: the Cannizzaro reaction – Be sure of the structure of the product – Systematic structural variation – The Hammett relationship – Other kinetic evidence for reaction mechanisms – Acid and base catalysis – The detection of intermediates – Stereochemistry and mechanism – Summary of methods for the investigation of mechanism.

 

MODULO 3. Retrosintesi e Stereoselettività

 28. Retrosynthetic analysis

Creative chemistry – Retrosynthetic analysis: synthesis backwards – Disconnections must correspond to known, reliable reactions – Synthons are idealized reagents – Multiple step syntheses: avoid chemoselectivity problems – Functional group interconversion – Two-group disconnections are better than one-group disconnections – C–C disconnections – Available starting materials – Donor and acceptor synthons – Two-group C–C disconnections – 1,5-Related functional groups – “Natural reactivity” and “umpolung”.

 31. Saturated heterocycles and stereoelectronics

Introduction – Reactions of saturated heterocycles – Conformation of saturated heterocycles: Heteroatoms in rings have axial and equatorial lone pairs – Some substituents of saturated heterocycles prefer to be axial: the anomeric effect – The anomeric effect in spiroketals – Related effects in other types of compounds – Making heterocycles: ring-closing reactions – Diastereotopic groups.

 32. Stereoselectivity in cyclic molecules

Introduction – Stereochemical control in six-membered rings – Reactions on small rings – Regiochemical control in cyclohexene epoxides – Stereoselectivity in bicyclic compounds – Fused bicyclic compounds – Spirocyclic compounds – Reactions with cyclic intermediates or cyclic – transition states.

 33. Diastereoselectivity

Looking back – Prochirality – Additions to carbonyl groups can be diastereoselective even without rings – Stereoselective reactions of acyclic alkenes – Aldol reactions can be stereoselective – Single enantiomers from diastereoselective reactions.

 41. Asymmetric synthesis

Nature is asymmetric – The chiral pool: Nature’s chiral centers “off the shelf” – Resolution can be used to separate enantiomers – Chiral auxiliaries – Chiral reagents – Asymmetric catalysis – Asymmetric formation of carbon-carbon bonds – Asymmetric aldol reactions.

The teaching material distributed by the teacher can be found on Studium at the following link.

1. Organic Chemistry – P. Y. Bruice – 8ª Ed. Pearson.
2. Organic Chemistry – J. Clayden, N. Greeves, and S. Warren – 2^nd Ed. Oxford University Press.
3. Solutions Manual to Accompany Organic Chemistry – J. Clayden, N. Greeves, and S. Warren – 2^nd Ed. Oxford University Press.

To pass the course, the student will have to take an unstructured written test and an oral test; the oral exam is accessed by scoring a minimum of 18 out of 35 points in the written exam.

The written test, lasting one hour and forty-five minutes (1:45), consists of 7 questions with a closed stimulus and an open answer, each with a maximum value of 5 points, covering the entire program. The written test will be considered passed with a minimum score of 18/35.

It is not allowed to consult books, notes, or electronic devices during the examination.

The oral exam consists of a discussion lasting about 45-60 minutes, aimed at ascertaining the level of knowledge and understanding reached by the student on the theoretical and methodological contents indicated in the program. The oral exam will also allow for verification of the student’s communication skills with properties of language and autonomous organization of the exposition on the same theoretical topics.

The student will be asked to explain some topics in detail and to carry out the retrosynthetic analysis of small molecules using the different approaches presented during the lessons. The student will have to demonstrate knowledge of the general approach to solving a synthetic problem and be able to design an adequate synthesis considering stereochemical issues. Theoretical principles will be discussed, and the ability of a rational application to practical problems will be evaluated. The student’s ability to analyze different synthetic ways to obtain the same product and the critical spirit developed thanks to a robust acquisition of the theoretical principles covered during the course will be evaluated.

The oral exam ends with an evaluation out of thirty to whose numerical formulation the following elements contribute:

• preparation on the entire program carried out;
• ability and clarity of presentation;
• ability to link and synthesize various topics.

The final grade will be established considering the scores achieved on both tests. It is essential to underline that the oral examination should not be understood as raising the grade obtained in the written test, but if it is negative, the grade may be lowered to the point of failing.

Passing the exam with minimum marks requires sufficient knowledge of the topics covered in the various parts of the program. To achieve a 30/30 cum laude, the student must demonstrate that he has acquired an excellent knowledge of all the topics covered during the course and can connect them logically.

An example of unstructured verification is available at the following link.